Vertebral metastases from neuroendocrine tumours: How to avoid false positives on 68Ga-DOTA-TOC PET using CT pattern analysis?

OBJECTIVES: To develop criteria to improve discrimination between vertebral metastases from neuroendocrine tumours (NETs) and benign bone lesions on PET combined with CT using DOTA-D-Phe1-Tyr3-octreotide labelled with gallium-68 (68Ga-DOTA-TOC). METHODS: In 535 NET patients, 68Ga-DOTA-TOC PET/CT examinations were reviewed retrospectively for vertebral CT lesions and/or PET foci. For each vertebral PET abnormality, appearance on CT, biological volume (BV), standardized uptake value (SUVmax) and ratios to those of reference organs were determined. All vertebral abnormalities were characterized as a metastasis, a typical vertebral haemangioma (VH) or other benign lesion. RESULTS: In 79 patients (14.8 %), we found 107 metastases, 34 VHs and 31 other benign lesions in the spine. The optimal cut-off values to differentiate metastases from benign lesions were BV ≥0.72 cm3, SUVmax ≥2, SUVmax ratio to a reference vertebra ≥2.1, to liver ≥0.28 and to spleen ≥0.14. They corresponded to lesion-based 68Ga-DOTA-TOC PET/CT sensitivity of 87 %, 98 %, 97 %, 99 % and 94 %, and specificity of 55 %, 100 %, 90 %, 97 %, 100 %, respectively. CONCLUSIONS: The high sensitivity of 68Ga-DOTA-TOC-PET/CT in detecting NET vertebral metastases was confirmed; this study showed that specificity could be improved by combining CT features and quantifying 68Ga-DOTA-TOC uptake. KEY POINTS: • Bone metastases in neuroendocrine tumours correlate with prognosis. • Benign bone lesions may mimic metastases on 68 Ga-DOTA-TOC PET/CT imaging. • The specific polka-dot CT pattern may be missing in some vertebral haemangiomas. • Lesion atypical for haemangiomas can be better characterized by quantifying 68 Ga-DOTA-TOC uptake.

68Ga-DOTATOC PET/CT in detecting neuroendocrine tumours responsible for initial or recurrent paraneoplastic Cushing's syndrome.

PURPOSE: Paraneoplastic Cushing's syndrome (PCS) is frequently caused by neuroendocrine tumours (NETs). Approximately 20% of tumours are still occult years later. Gallium-68 somatostatin receptor-PET/CT is promising for the detection of the causal primary NET, but its role in case of recurrent PCS is rarely reported. We report our experience with DOTATOC PET/CT in localising the causal NET in cases of initial but also recurrent PCS, and its clinical impact. METHODS: A retrospective review of all DOTATOC PET/CTs performed in consecutive patients referred for PCS to our centre, between January 2011 and June 2017, was done. Nineteen patients underwent 26 PET/CTs, 13 for detection of a primary NET, seven for persistent or recurrent PCS after resection, and six for surveillance after resection of NETs previously detected on a DOTATOC PET/CT in our centre. RESULTS: Among the 13 PET/CTs performed to search for primary NET, five were positive: four carcinoid lung tumours were confirmed after resection and one lung focus was not confirmed since surgery would have carried a high risk. Clinical impact was 23% (3/13). Among the seven PET/CTs performed for persistent or recurrent PCS, six were true-positive, with confirmation of metastatic lymph nodes after resection. Clinical impact was 57% (4/7). All PET/CTs performed for surveillance were true-negative. CONCLUSIONS: DOTATOC PET/CT seems to be a valuable tool for detection of the NET responsible for persistent or recurrent PCS after surgery. In this context, DOTATOC PET/CT was more effective than for the detection of the causal tumour in initial PCS.

A Restless Leg Syndrome Incidentally Detected by an 18F-FDG Positron Emission Tomography.

A case of a restless leg syndrome (RLS) was incidentally detected in a 49-year-old woman referred for an F-FDG PET/CT in monitoring her breast cancer. She was treated with chemotherapy and on long-term hormone therapy. Diffuse F-FDG uptake of calf muscles was visualized. Medical history revealed that the patient felt leg cramps in supine position, suggesting RLS. The diagnosis was confirmed using clinical rating scales and polysomnography. RLS being underdiagnosed, this type of FDG PET/CT incidental finding should prompt to check the presence of evocative symptoms and refer the patient to a physician specialized in sleep disorders.

Generalized Lymph Node FDG Uptake as the First Manifestation of Systemic Lupus Erythematosus.

We report 2 cases of young patients referred for FDG PET/CT for peripheral lymphadenopathy and moderate fever associated with pericarditis in 1 patient and glomerulonephritis in the other patient. FDG PET/CT showed a very similar appearance in these 2 patients, with highly avid lymph nodes with axillary predominance and diffuse FDG uptake in spleen and bone marrow. Systemic lupus erythematosus with an unusual presentation of generalized lymphadenopathy was diagnosed in both patients. This FDG distribution pattern should be kept in mind when PET is performed for etiological investigation of fever of unknown origin.

Silicone Granuloma in the Buttocks Incidentally Detected by 18F-FDG PET/CT 30 Years After Free Liquid Silicone Injections.

A 59-year-old transexual (male to female) patient presented with a squamous cell carcinoma of the larynx. She underwent an F-FDG PET/CT for initial staging. The examination showed high F-FDG uptake of the primary lesion and a homolateral lymphadenopathy. Incidental heterogeneous uptake of round hyperdense lesions in the gluteal muscles and subcutaneous fat was visualized. The medical history revealed secondly that the patient had had free liquid silicone injections 30 years before the examination. Although the injection of free silicone is not practised since the 1980s, this incidental finding should prompt to check the patient's medical history over several decades.

A Pilot Comparison of 18F-fluorocholine PET/CT, Ultrasonography and 123I/99mTc-sestaMIBI Dual-Phase Dual-Isotope Scintigraphy in the Preoperative Localization of Hyperfunctioning Parathyroid Glands in Primary or Secondary Hyperparathyroidism: Influence of Thyroid Anomalies.

We compared (18)F-fluorocholine hybrid positron emission tomography/X-ray computed tomography (FCH-PET/CT) with ultrasonography (US) and scintigraphy in patients with hyperparathyroidism and discordant, or equivocal results of US and (123)I/(99m)Tc-sesta-methoxyisobutylisonitrile (sestaMIBI) dual-phase parathyroid scintigraphy. FCH-PET/CT was performed in 17 patients with primary (n = 11) lithium induced (n = 1) or secondary hyperparathyroidism (1 dialyzed, 4 renal-transplanted).The reference standard was based on results of surgical exploration and histopathological examination. The results of imaging modalities were evaluated, on site and by masked reading, on per-patient and per-lesion bases.In a first approach, equivocal images/foci were considered as negative. On a per-patient level, the sensitivity was for US 38%, for scintigraphy 69% by open and 94% by masked reading, and for FCH-PET/CT 88% by open and 94% by masked reading. On a per-lesion level, sensitivity was for US 42%, for scintigraphy 58% by open and 83% by masked reading, and for FCH-PET/CT 88% by open and 96% by masked reading. One ectopic adenoma was missed by the 3 imaging modalities. Considering equivocal images/foci as positive increased the accuracy of the open reading of scintigraphy or of FCH-PET/CT, but not of US. FCH-PET/CT was significantly superior to US in all approaches, whereas it was more sensitive than scintigraphy only for open reading considering equivocal images/foci as negative (P = 0.04). FCH uptake was more intense in adenomas than in hyperplastic parathyroid glands. Thyroid lesions were suspected in 9 patients. They may induce false-positive results as in one case of oncocytic thyroid adenoma, or false-negative results as in one case of intrathyroidal parathyroid adenoma. Thyroid cancer (4 cases) can be visualized with FCH as with (99m)Tc-sestaMIBI, but the intensity of uptake was moderate, similar to that of parathyroid hyperplasia.This pilot study confirmed that FCH-PET/CT is an adequate imaging tool in patients with primary or secondary hyperparathyroidism, since both adenomas and hyperplastic parathyroid glands can be detected. The sensitivity of FCH-PET/CT was better than that of US and was not inferior to that of dual-phase dual-isotope (123)I/(99m)Tc-scintigraphy. Further studies should evaluate whether FCH could replace (99m)Tc-sestaMIBI as the functional agent for parathyroid imaging, but US would still be useful to identify thyroid lesions.

Role of SPECT/CT in sentinel lymph node detection in patients with breast cancer.

AIM: The purpose of this study was to conduct a systematic review of the published literature to assess the role (indications, advantages, and limitations) of SPECT/CT for the detection of sentinel lymph node (SLN) in breast cancer. METHODS: The authors searched PubMed for published literature in English addressing this topic. RESULTS: Eleven studies, published since 2006, focused on the role and value of SPECT/CT for SLN detection (SLND). They showed that SPECT/CT improved sentinel node detection and anatomical localization. One study suggested that SPECT/CT may provide a more accurate staging. Limitations for SLND with SPECT/CT include extra time and inconvenience for the patient and additional radiation dose. CONCLUSIONS: SPECT/CT is a valuable tool for SLND, especially in difficult cases, when planar lymphoscintigraphy shows no SLN or unexpected lymphatic drainage.

Is 18F-fluorocholine-positron emission tomography/computerized tomography a new imaging tool for detecting hyperfunctioning parathyroid glands in primary or secondary hyperparathyroidism?

CONTEXT: Preoperative ultrasonography and scintigraphy using (99m)Tc-sestamibi are commonly used to localize abnormal parathyroid glands. In cases of discrepant results between scintigraphy and ultrasonography, it is important to rely on another diagnostic imaging modality. (18)F-fluorodeoxyglucose (FDG) and (11)C-methionine positron emission tomography (PET) have been studied, but are imperfect to detect abnormal parathyroid glands. Recently, first cases of abnormal parathyroid glands taking-up radiolabelled choline were discovered incidentally in men referred to (11)C-choline or (18)F-fluorocholine (FCH)-PET/CT for prostate cancer. We checked if FCH uptake was a general feature of adenomatous or hyperplastic parathyroid glands. METHODS: FCH-PET/CT was performed in 12 patients with primary (n = 8) or secondary hyperparathyroidism (1 dialyzed, 3 grafted) and with discordant or equivocal results on preoperative ultrasonography (US) and/or (123)I/(99m)Tc-sestamibi dual-phase scintigraphy. The results of the FCH-PET/CT were evaluated, with surgical exploration and histopathologic examination as the standard of truth. RESULTS: On a per-patient level, the detection rate of FCH-PET/CT (at least one FCH focus corresponding to an abnormal parathyroid gland in a given patient) was 11/12 = 92%. FCH-PET/CT detected 18 foci interpreted as parathyroid glands and correctly localized 17 abnormal parathyroid glands (7 adenomas and 10 hyperplasias). On a per-lesion level, FCH-PET/CT results were 17 TP, 2 false negative ie, a lesion-based sensitivity of 89%, and 1 false positive. CONCLUSION: As the main result of this pilot study, we show that in patients with hyperparathyroidism and with discordant or equivocal results on scintigraphy or on ultrasonography, adenomatous or hyperplastic parathyroid glands can be localized by FCH-PET/CT with good accuracy. Furthermore, FCH-PET/CT can solve discrepant results between preoperative ultrasonography and scintigraphy and has thus a potential as a functional imaging modality in the detection of abnormal parathyroid glands. Our preliminary results are encouraging and prompt us to further evaluate FCH-PET/CT as a functional imaging agent in patients with biochemical hyperparathyroidism.

¹8F-FDG-PET/CT in staging, restaging, and treatment response assessment of male breast cancer.

PURPOSE: Male breast cancer (BC) is a rare disease, with patterns different from those found in women. Most tumors are detected at more advanced stages than in women. The aim of this study was to analyze the performance of [18F]fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG-PET/CT) in staging, restaging, and therapy response assessment. METHODS: We performed a systematic analysis in the database of Saint-Louis Hospital to identify male patients with BC referred for PET/CT. (18)F-FDG-PET/CT findings considered suspicious for malignancy were compared to biopsy results, further work-up and/or patient follow-up of at least 6 months. Performances of (18)F-FDG-PET/CT were compared to that of conventional imaging (CI) using the McNemar test. The impact of PET/CT on management was evaluated. RESULTS: During 6 consecutive years, among 12,692 (18)F-FDG-PET/CT oncology studies, 30 were performed in 15 men with BC: 7 examinations for initial staging, 11 for restaging, and 12 for response assessment. Tumors profile was ER+ and one had HER2 overexpression. PET/CT sensitivity, specificity, positive predictive value, negative predictive value and accuracy to detect distant metastases were 100%, 67%, 86%, 100% and 89%, respectively. PET/CT was more informative than CI in 40% of studies (p=0.03; 95% confidence interval: 3.26 - 40%). Findings from (18)F-FDG-PET/CT led to modification in the planned treatment in 13/30 cases (43%). CONCLUSION: Although all the tumors were ER+, primary lesions and metastases were diagnosed with high sensitivity. (18)F-FDG-PET/CT seems to be a powerful imaging method to perform staging, restaging and treatment response assessment in male patients with BC.

Strengths and limitations of using 18fluorine-fluorodihydroxyphenylalanine PET/CT for congenital hyperinsulinism.

18fluorine-fluorodihydroxyphenylalanine (FDOPA) PET/CT is currently the first-line imaging technique to distinguish between focal and diffuse forms of congenital hyperinsulinism (CHI) and to accurately localize focal forms. However, this technique has a number of limitations, mainly the very small size of focal forms or inversely a very large focal form mimicking a diffuse form, and misinterpretation of physiologic uptake masking hot spots or inversely mimicking focal forms. The other limitation is the limited availability of the radiopharmaceutical. FDOPA PET/CT has no recognized competitor to date among the available morphologic and functional imaging techniques. Other potential approaches using specific tracers for positron emission tomography (PET) are discussed, using radiopharmaceuticals specific for ß cell mass or targeting somatostatin receptors. These radiopharmaceuticals can be labeled with gallium-68, a PET emitter readily available in PET centers equipped with 68Ge/68Ga generators.

Can we achieve a radionuclide radiation dose equal to or less than that of 99mTc-hydroxymethane diphosphonate bone scintigraphy with a low-dose 18F-sodium fluoride time-of-flight PET of diagnostic quality?

PURPOSE: 18F-Sodium fluoride is a bone tracer with a high signal-to-noise ratio, but its dosimetry is higher than that of 99mTc-labeled phosphonates at the recommended activities. The study's purpose was to determine whether the reduction by half of F-sodium fluoride-injected activity, mimicked by a short-timed reconstruction image, simulating a total dose less than or equal to that of 99mTc-hydroxymethane diphosphonate scintigraphy, had an impact on the accuracy of PET semiquantitative measurements and image quality. METHODS: Whole-body time-of-flight 18F-sodium fluoride PET/computed tomography (CT) images were acquired prospectively from 40 adult patients for detection of bone metastases. 18F-Sodium fluoride was administered according to the European Association of Nuclear Medicine (EANM) and Society of Nuclear Medicine (SNM) practice guidelines. From the acquired 1 min/bed position list-mode data, 30-s reconstructions were extracted. Measurements of maximum standard uptake value were recorded with a region of interest applied to the same location on the 1-min and 30-s images, which were displayed side by side, and were analyzed using Bland-Altman plots. A masked reading was performed by two senior nuclear medicine physicians who counted the foci of visually increased uptake. RESULTS: Bland-Altman plots showed an excellent agreement between the maximum standard uptake value measurements of the 60- and 30-s images. The paired Wilcoxon test results between the corresponding 60- and 30-s images read by masked readers A and B were not significant (P=0.15 and 0.19, respectively). CONCLUSION: Reducing acquisition duration by half or injecting half of the activity recommended by the EANM and SNM practice guidelines can lead to 18F-sodium fluoride time-of-flight PET images of diagnostic quality, achieving a radiation dose less than or equal to that of 99mTc-labeled phosphonates.